CAJ | 학술논문

目的观察4-氨基水杨酸(4-ASA)对三硝基苯磺酸(TNBS)诱导的大鼠实验性结肠炎炎症损伤、肠组织一氧化氮合酶(iNOS)表达、血中性粒细胞(PMN)凋亡及血清白细胞介素(IL)-8水平等的影响,探讨4-ASA对炎症性肠病(IBD)的治疗作用及机制.方法 40只SD大鼠分为正常对照组(n=10)和实验组(n=30),实验组建立大鼠结肠炎模型.建模第5天将实验组按照处理方式分为实验对照组(n=10,0.9%氯化钠1 ml灌肠),5-ASA组[n=10,5-ASA液(200 mg/kg)1 ml灌肠]和4-ASA组[n=10,4-ASA液(200 mg/kg)1 ml灌肠].连续治疗7 d后处死动物,取病变段肠组织,行结肠大体损伤及结肠组织学损伤评分;生化法检测髓过氧化物酶活性;免疫组化法检测肠组织iNOS表达量;流式细胞术检测血PMN凋亡率;酶联免疫吸附法检测血清IL-8浓度.结果经4-ASA治疗7d后,4-ASA组大鼠体重明显较实验对照组增加(P<0.01,t=14.09);疾病活动指数评分、大体评分、组织学评分和MPO活性显著较实验对照组降低(t值分别=7.87、18.37、6.66和19.60,P值均<0.01).而5-ASA组与4-ASA组间上述各指标差异均无统计学意义(P值均>0.05).实验对照组肠组织iNOS表达率为(73.55±5.15)%,较正常对照组显著增加[(5.95±1.45)%,t=39.93,P<0.01)];5-ASA和4-AsA组大鼠肠组织iNOS表达率分别为(37.80±3.82)%和(42.27±3.52)%,均较实验对照组显著降低(t值分别=17.62和15.76,P值均<0.01).实验对照组血清IL-8的平均浓度明显高于正常对照组(t=25.25,P<0.01);5-ASA和4-ASA组明显低于实验对照组(t值分别=12.31和11.57,P值均<0.01).实验对照组血PMN凋亡率明显低于正常对照组(t=11.48,P<0.01);5-ASA和4-ASA组凋亡率明显高于实验对照组(t值分别=7.51和10.47,P值均<0.01).结论 4-ASA灌肠对实验性结肠炎大鼠具有显著的治疗作用,其治疗机制可能与降低PMN的趋化与激活、上调血PMN凋亡率、减少肠组织局部损伤因子有关.
목적 관찰4-안기수양산(4-ASA)대삼초기분광산(TNBS)유도적대서실험성결장염염증손상、장조직일양화담합매(iNOS)표체、혈중성립세포(PMN)조망급혈청백세포개소(IL)-8수평등적영향,탐토4-ASA대염증성장병(IBD)적치료작용급궤제.방법 40지SD대서분위정상대조조(n=10)화실험조(n=30),실험조건립대서결장염모형.건모제5천장실험조안조처리방식분위실험대조조(n=10,0.9%록화납1 ml관장),5-ASA조[n=10,5-ASA액(200 mg/kg)1 ml관장]화4-ASA조[n=10,4-ASA액(200 mg/kg)1 ml관장].련속치료7 d후처사동물,취병변단장조직,행결장대체손상급결장조직학손상평분;생화법검측수과양화물매활성;면역조화법검측장조직iNOS표체량;류식세포술검측혈PMN조망솔;매련면역흡부법검측혈청IL-8농도.결과 경4-ASA치료7d후,4-ASA조대서체중명현교실험대조조증가(P<0.01,t=14.09);질병활동지수평분、대체평분、조직학평분화MPO활성현저교실험대조조강저(t치분별=7.87、18.37、6.66화19.60,P치균<0.01).이5-ASA조여4-ASA조간상술각지표차이균무통계학의의(P치균>0.05).실험대조조장조직iNOS표체솔위(73.55±5.15)%,교정상대조조현저증가[(5.95±1.45)%,t=39.93,P<0.01)];5-ASA화4-AsA조대서장조직iNOS표체솔분별위(37.80±3.82)%화(42.27±3.52)%,균교실험대조조현저강저(t치분별=17.62화15.76,P치균<0.01).실험대조조혈청IL-8적평균농도명현고우정상대조조(t=25.25,P<0.01);5-ASA화4-ASA조명현저우실험대조조(t치분별=12.31화11.57,P치균<0.01).실험대조조혈PMN조망솔명현저우정상대조조(t=11.48,P<0.01);5-ASA화4-ASA조조망솔명현고우실험대조조(t치분별=7.51화10.47,P치균<0.01).결론 4-ASA관장대실험성결장염대서구유현저적치료작용,기치료궤제가능여강저PMN적추화여격활、상조혈PMN조망솔、감소장조직국부손상인자유관.
Objective To investigate the effects of 4-aminosalicylic acid (4-ASA) on rats with 2,4,6-trinitrobenzenesulfonic acid-induced colitis in order to understand its mechanisms in treatment of inflammatory bowel disease (IBD). Methods Thirty SD rats were given 2,4,6-trinitrobenzenesulfonic acid to induce colitis and were divided into model group, 5-ASA (200 mg/kg) treated group and 4-ASA (200 mg/kg) treated group with 10 each. Another 10 rats were severed as normal control. Seven days later,all animals were sacraficed for estimation of colonic tissues. The iNOS and serum level of interleukin (IL)-8 were detected by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) ,respectively. And the apoptosis of polymorphonuclear neutrophil (PMN) was examined by flow cytometry. Results In comparison with model group, the body weight was increased in rats treated with 4-ASA (t= 14.09,P<0.01), whereas the macroscopic and histological scores and MPO activity were decreased (t=7.87,18.37,6.66 and 19.60,respectively, all P values <0.01), which were similar to 5-ASA treated group (all P values > 0. 05). The expression of tissue iNOS was 73.55%±5.15% in model group, which was higher than that in control group [(5.95±1.45)% ,t=39.93,P<0.01)],but was lower than that in 5-ASA treated group [(37.80±3.82)%,t = 17.62,P<0.01] and 4-ASA treated group [(42.27±3.52) %, t= 15.76 ,P<0.01]. The serum level of IL-8 in model group was significantly higher than that in 5-ASA treated group and 4-ASA treated group (P<0. 01). The apoptosis of PMN in model group was lower than that in control group (t= 11.48,P<0.01), but higher than that in 5-ASA treated group (t= 7.51, P<0.01) and 4-ASA treated group (t= 10.47,P<0.01). Conclusions The efficacy of 4-ASA in treatment of IBD may be related to the mechanisms of reducing the migration and the activities of PMN, up-regulating PMN apoptosis and scavenging reactive oxygen radicals produced by PMN.